A flexible test for early-stage studies with multiple endpoints.

This paper builds on the recently proposed prediction test for muliple endpoints. The prediction test combines information across multiple endpoints while accounting for the correlation between them. The test performs well with small samples relative to the number of endpoints of interest and is flexible in the hypotheses across the individual endpoints that can be combined. The prediction test addresses a global hypothesis that is of particular interest in early-stage studies and can be used as justification for continuing on to a larger trial. However, the prediction test has several limitations which we seek to address. First, the prediction test is overly conservative when both the effect sizes across all endpoints and the number of endpoints are small. By using a parametric bootstrap to estimate the null distribution, we show that the test achieves the nominal error rate in this situation and increases the power of the test. Second, we provide a framework to allow for predictions of a difference on one or more endpoints. Finally, we extend the test with a composite null hypothesis that allows for different null hypothesized predictive abilities across the endpoints which can be especially useful if the study contains both familiar and novel endpoints. We use an example from a physical activity trial to illustrate these extensions.

Representation of Racial and Ethnic Minority Populations in Dementia Prevention Trials: A Systematic Review.

Despite older racial and ethnic minorities (REMs) being more likely to develop dementia they are underrepresented in clinical trials focused on neurological disorders. Inclusion of REMs in dementia prevention studies is vital to reducing the impact of disparities in dementia risk. We conducted a systematic review to characterize the number of REM enrolled in brain health and prevention randomized controlled trials (RCTs). RTCs published from January 1, 2004 to April 21, 2020 were included. Participants were normal cognitive adults aged 45 years and older who participated in a Phase II or Phase III U.S. based preventative trial. Analyses were performed to examine differences in trial characteristics between RCTs that did and those that did not report race/ethnicity and to calculate the pooled proportion of each racial/ethnic group in randomized brain healthy prevention trials. A total of 42 studies consisting of 100,748 participants were included in the final analyses. A total of 26 (62%) reported some racial/ethnic identity data. The pooled proportion of REM participants was 0.256 (95% CI, 0.191, 0.326). There is a lack of racial/ethnic reporting of participants and REMs remain underrepresented in brain health prevention RCTs.

Evaluating Paired Categorical Data when the Pairing is Lost.

We encountered a problem in which a study's experimental design called for the use of paired data, but the pairing between subjects had been lost during the data collection procedure. Thus we were presented with a data set consisting of pre and post responses but with no way of determining the dependencies between our observed pre and post values. The aim of the study was to assess whether an intervention called Self-Revelatory Performance had an impact on participant's perceptions of Alzheimer's disease. The participant's responses were measured on an Affect grid before the intervention and on a separate grid after. To address the underlying question in light of the lost pairing we utilized a modified bootstrap approach to create a null hypothesized distribution for our test statistic, which was the distance between the two Affect Grids' Centers of Mass. Using this approach we were able to reject our null hypothesis and conclude that there was evidence the intervention influenced perceptions about the disease.

Comparing methods to identify hip fracture in a nursing home population using Medicare claims.

UNLABELLED: The inpatient principal diagnosis in Medicare claims identified 96% of hip fractures in hospitalized nursing home residents with high rates of confirmation by other claims files. INTRODUCTION: Hip fracture is typically identified in Medicare claims by examining only the principal diagnosis in the inpatient file, but this simple approach might be inadequate for nursing home residents. Our objective was to examine the impact of varied operational definitions for identifying hip fracture hospitalizations in administrative claims data. METHODS: We conducted a retrospective examination of Medicare inpatient and outpatient claims data for dually Medicaid- and Medicare-eligible nursing home residents in 1999 in California, Florida, Missouri, New Jersey, and Pennsylvania (n = 197,514). We determined the number of hip fractures identified in inpatient (Medicare A) diagnoses codes using differing definitions that varied according to whether or not hip fracture was required to be the principal diagnosis and whether or not confirmatory imaging and procedure codes were required to be found in other (Medicare B) claims files. RESULTS: Hip fractures were found in any inpatient diagnosis position in 4,680 subjects, with 4,479 of these found in the principal diagnosis position. With either approach to diagnosis position, confirmatory imaging and procedure codes were identified for 95% of persons hospitalized with hip fracture. CONCLUSION: The principal diagnosis alone will identify 96% of hip fracture diagnoses in hospitalized nursing home residents. Such diagnoses are confirmed at very high rates by other sources of claims data. Researchers may be confident using a simple approach to identifying hip fracture hospitalizations in this population, using inpatient claims alone and interrogating only the principal diagnosis position.

Rural nursing and health care reforms: building a social model of health.

This article explores recent shifts in health-care policy and the implications for rural nursing in Australia. Health-care reforms have resulted in the implementation of a 'market forces' ideology, creating tensions between economic imperatives and the need for equity and greater access in rural service delivery. New models of health-service delivery have been developed that have significant implications for the way rural health care is defined, practised and received. The issues surrounding the context of rural nursing practice and service delivery are discussed.

Predictors of the development of hyperkalemia in patients using angiotensin-converting enzyme inhibitors.

BACKGROUND/AIMS: Angiotensin-converting enzyme inhibitors (ACEI) are the antihypertensives of choice in patients with chronic renal failure (CRF). ACEI by decreasing the synthesis of aldosterone, the main regulator of serum potassium, predispose to the development of hyperkalemia. Although hyperkalemia with administration of ACEI is uncommon in patients with a normal renal function, a preexisting abnormality in potassium hemostasis, as seen in patients with chronic renal failure, may increase the risk of hyperkalemia. METHOD: To determine the predictors of development of hyperkalemia (K >5.1 mEq/l) in patients on ACEI, we retrospectively reviewed medical records of 119 patients followed in our renal clinic. RESULTS: The mean age of the patients was 56 +/- (SD) 13 (range 20-84) years. Sixty-three percent were males, and 37% were females. Sixty-seven percent had a history of diabetes. Eighty five percent of the patients had CRF [creatinine clearance (CrCl) <80 ml/min]. The baseline serum Cr was 2.3 +/- 1.2 (range 0.6-6.9) mg/dl, and the CrCl was 50 +/- 27.5 ml/min. Of the 119 patients 46 (38.6%) developed hyperkalemia (mean K 5.68 +/- 0.3, range 5.2-6.7 mEq/l). Ninety-six percent of the patients who developed hyperkalemia had CRF, and 84% were diabetics. Pearson product-moment correlation revealed a significant positive correlation of hyperkalemia with Cr and a negative correlation of hyperkalemia with CrCl and HCO(3) (Cr: r = 0.42, p < 0.0001; CrCl: r = -0.34, p < 0.0001; HCO(3): r = -0.41, p < 0.0001). Multivariate logistic regression analysis revealed diabetes and serum creatinine to be the main predictors of hyperkalemia. In 31 patients hyperkalemia resolved either with a low-potassium (2 g/day) diet or with diet and a decrease in the dose of ACEI. In 15 patients ACEI had to be discontinued due to persistent hyperkalemia. CONCLUSIONS: We conclude that hyperkalemia is common in patients with CRF on ACEI. The majority of the patients who develop hyperkalemia on ACEI have CRF and diabetes. A large number of patients with CRF require discontinuation of ACEI due to hyperkalemia and are deprived of their renoprotective effects.